Several experimental models of epilepsy have used kainic acid in animals to induce seizures and neuropathological changes which mimic those observed in human temporal lobe epilepsy. These models differ in the location and manner in which kainic acid is applied. In the present study, we characterized the seizure activity and neuropathological changes that occur in awake rats after kainic acid (25 ng/250 nl) is injected into the entorhinal cortex of freely moving rats. In 91% of the animals, this induced generalized motor seizures. Moreover, all of the animals survived status epilepticus. Animals were perfused two weeks after the injection for neuropathological examination. Silver-impregnation revealed that kainic acid caused pyramidal cell damage which was most severe in the CA1 subfield and to a lesser degree in the CA3c area. A loss of NADPH diaphorase-containing neurons in the hilus and the CA1 area was also consistently seen and, in most cases, a population of somatostatin-immunoreactive neurons was diminished. Our findings show that a minute amount of kainic acid delivered directly to the entorhinal cortex on unanesthetized animals reliably produces generalized seizures as well as a consistent pattern of cell damage in the hippocampus. Therefore, this model may be suitable for investigating the mechanisms underlying temporal lobe epilepsy, and may prove useful in assessing different treatment strategies for preventing seizure-induced structural damage.